PROCAARE: Cytotoxic T cell responses in early HIV infection

[procaare@usa.healthnet.org]

Reference: Musey, L., Hughes, J., Schacker, T., Shea, T., Corey, L.,
McElrath, M.J. (1997).  Cytotoxic-T-cell responses, viral load, and
disease progression in early human immunodeficiency virus type I
infection.  New Engl. J. Med. 337: 1267-74.

This prospective study enrolled 33 patients with primary HIV-1 infection,
and examined cytotoxic T cell responses longitudinally over 18-24 months.
Median time of enrollment was 55 days following infection, and median CD4
count was 568/mm3.  No participant received antiretroviral therapy during
primary infection; 15% received therapy during follow-up.

Peripheral blood mononuclear cells were enriched for T cell subsets and
were incubated with target cells (autologous Epstein-Barr transformed
lymphoblastoid lines infected with vaccinia virus constructs expressing
HIV-1 or control gene products).  The identification of specific cytotoxic
T cell responses was established in standard chromium release assays with
target and effector cells.   The frequencies of precursor (or memory)
cytotoxic T cells were estimated in a limiting dilution chromium release
assay.   

HIV-1-specific cytotoxic T cells were found in 17 of the 33 patients (74%)
soon after primary infection.  The HIV Env protein was most commonly
recognized (94% of reponsive patients), with less frequent recognition of
Gag and Pol (29% and 12%, respectively).  Memory cytotoxic T cells were
detected in 6 of 6 individuals tested during the first three months of
infection and 17 of 21 studied during the first six months.  There was
considerable individual variation in memory responses with time, though
there was a general decline during the first 6-8 months of HIV infection,
with a plateau during the ensuing 1-1.5 years.  

Patients with higher frequencies of Env-specific cytotoxic T cells had
significantly lower plasma viral loads than those with lower cytotoxic T
cell responses (22,000 vs. 62,000  p=0.006).  Among 19 patients in which
memory responses were assayed, 80% with Env-specific reponses in early
infection maintained CD4 counts >300/mm3, compared to 44% of those lacking
Env cytotoxic T cell recognition (p=0.05).
Although these differences are relatively modest in view of those
achievable by combination antiretroviral therapy, further study of the
role of cytotoxic T lymphocyte responses in the control of early HIV
infection may well yield insights for following disease progression or for
the design of new therapeutic interventions.

KEYWORDS: BASIC SCIENCE, CYTOTOXIC T CELL, MEMORY T CELL, CHROMIUM
RELEASE, ENV, GAG, POL, DISEASE PROGRESSION 

From: Albert Shaw <ashaw@usa.healthnet.org>
--
Send mail for the `ProCAARE' conference to `procaare@usa.healthnet.org'.
Mail administrative requests to `majordomo@usa.healthnet.org'.
For additional assistance, send mail to:  `owner-procaare@usa.healthnet.org'.